AJP - Renal Physiology, Vol 255, Issue 6 1107-F1115, Copyright © 1988 by American Physiological Society
Tonic inhibition of renal response to vasopressin by a pertussis toxin substrate
W. B. Jeffries, R. Fallet, G. D. Gong, P. Van Dreal and W. A. Pettinger
Department of Pharmacology, University of Texas Health Science Center, Dallas 75235.
The putative role of the inhibitory guanine nucleotide binding protein (Gi)
in modulating the renal response to vasopressin was investigated using
islet activating protein (IAP). IAP treatment in rats in vivo abolished the
capacity of alpha 2-adrenoceptors to reverse vasopressin-induced adenosine
3',5'-cyclic monophosphate (cAMP) accumulation in microdissected cortical
collecting tubule (CCT) segments. IAP pretreatment also caused a marked
upward shift in the dose-response curve of vasopressin (10(-10) to 10(-4)
M)-induced cAMP accumulation. Augmentation of the response to vasopressin
in rat CCT was dependent on the in vivo dose of IAP and paralleled the loss
in alpha 2-adrenoceptor responsiveness. In the isolated perfused kidney the
antinatriuretic and antidiuretic effects of the V2-receptor agonist
desamino-8-D-arginine vasopressin (DDAVP) (1 pM) were enhanced following
IAP pretreatment. alpha 2-Adrenoceptor stimulation (30 nM epinephrine)
inhibited the renal effects of DDAVP (1 pM) in kidneys from control but not
IAP-pretreated rats. Interestingly, IAP pretreatment alone caused increased
urine flow rate and enhanced excretion of sodium and chloride without
affecting potassium excretion or renal hemodynamics in vitro. Our results
suggest that an IAP substrate, probably Gi, 1) is required for signal
transduction by renal alpha 2-adrenoceptors, 2) may tonically modulate the
response to vasopressin in the CCT but not of parathyroid hormone in the
proximal convoluted tubule, and 3) participates in renal water and
electrolyte reabsorption independent of exogenous adenylate cyclase
stimulation.
